CARDIAC SODIUM-CHANNEL STRUCTURE AND FUNCTION

The upstroke of the action potential in heart cells, as in nerve and skeletal muscle cells, is due to the movement of sodium ions through ion-selective channels in the surface membrane. Voltage-dependent sodium channels in the heart, while sharing many common electrophysiologic characteristics with sodium channels in nerve and skeletal muscle, are distinctive in that they also contribute current to the plateau phase of the action potential and have unique sensitivities to channel-active toxins and drugs, most notably the local anesthetic-type antiarrhythmic agents. With the recent cloning and functional expression of the rat and human cardiac sodium channel genes, we are now in a position to understand better the molecular mechanisms responsible for the unique characteristics of sodium channels in the heart.